A Randomized Phase II Trial of ASTX727 and Venetoclax Compared With ASTX727, Venetoclax, and Enasidenib for Newly Diagnosed Older Adults With IDH2 Mutant Acute Myeloid Leukemia: A MyeloMATCH Substudy
National Cancer Institute (NCI)
Summary
This phase II MyeloMATCH treatment trial studies how well ASTX727 and venetoclax plus enasidenib works compared to ASTX727 and venetoclax alone for the treatment of older patients with newly diagnosed acute myeloid leukemia (AML) or younger patients who are considered unfit for standard treatment, and who have an abnormal change (mutation) in the IDH2 gene. This gene mutation can cause AML to grow and spread. This trial is being done to see if adding enasidenib to the usual treatment can help more patients with the IDH2 gene get rid of AML. ASTX727 is a fixed-dose formulation of two drugs, cedazuridine and decitabine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Enasidenib works by stopping the growth and spread of tumor cells that have the IDH2 mutation. Giving ASTX727 and venetoclax plus enasidenib may work better in treating AML patients with the IDH2 mutation.
Description
PRIMARY OBJECTIVES: I. To evaluate the safety of decitabine and cedazuridine (ASTX727) + venetoclax + enasidenib (Arm 2) before initiating randomization. II. To compare the rate of measurable residual disease (MRD) negative complete remission (CR) based on multiparameter flow cytometry (MFC) after two cycles of treatment in older adults (or unfit adults age 18 or older) with IDH2 mutated Acute Myeloid Leukemia (AML) who receive ASTX727, venetoclax, and enasidenib versus ASTX727 and venetoclax alone. SECONDARY OBJECTIVES: I. To estimate the composite remission rate (CR + complete remission…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Participants must have been registered to the MYELOMATCH Master Screening and Reassessment Protocol prior to consenting to this study. Participants must have disease with a detectable IDH2 mutation based on central testing through the MYELOMATCH and be assigned to this clinical trial via MATCHBox prior to registration to this study * Note: Pre-enrollment/diagnosis labs must have already been performed under MYELOMATCH * Participants must have newly diagnosed, untreated acute myeloid leukemia (AML) defined by having ≥ 20% blasts in the bone marrow and/or peripheral blo…
Interventions
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureBone Marrow Aspiration
Undergo bone marrow aspiration
- ProcedureBone Marrow Biopsy
Undergo bone marrow biopsy
- DrugDecitabine and Cedazuridine
Given PO
- DrugEnasidenib
Given PO
- DrugVenetoclax
Given PO
Locations (124)
- Banner University Medical Center - TucsonTucson, Arizona
- University of Arizona Cancer Center-North CampusTucson, Arizona
- University of Arkansas for Medical SciencesLittle Rock, Arkansas
- Alta Bates Summit Medical Center-Herrick CampusBerkeley, California
- Mills Health CenterSan Mateo, California
- Miami Cancer InstituteMiami, Florida